New Treatment of Periodontal Diseases by Using NF-κB Decoy Oligodeoxynucleotides via Prevention of Bone Resorption and Promotion of Wound Healing

Abstract

Nuclear factor-kappa B (NF-κB) is involved in osteoclast differentiation and activation. Thus, the blockade of the NF-κB pathway might be a novel therapeutic strategy for treating bone metabolic diseases. Periodontitis is subgingival inflammation caused by bacterial infection; this disease also is thought to be a chronic focal point responsible for systemic diseases. In this study, NF-κB decoy oligodeoxynucleotides (ODNs) were topically applied for experimental periodontitis in a debris-accumulation model and wound healing in a bone-defect model of beagle dogs to investigate the effect of decoy ODN on bone metabolism. Application of NF-κB decoy ODN significantly reduced interleukin-6 activity in crevicular fluid and improved alveolar bone loss in the analysis of dental radiographs and DEXA. Direct measurement of exposed root that lost alveolar bone support revealed that NF-κB decoy treatment dramatically protected bone from loss. In a bone-defect model, NF-κB decoy ODN promoted the healing process as compared with control scrambled decoy in micro-CT analysis. Overall, inhibition of NF-κB by decoy strategy prevented the progression of bone loss in periodontitis and promoted the wound healing in bone defects through the inhibition of osteoclastic bone resorption. Targeting of NF-κB might be a potential therapy in various bone metabolic diseases. Antioxid. Redox Signal. 11, 2065–2075.